Studies have been directed to whether bacteria, once having initiated the disease, are necessary for persistence of pathology in pyelonephritis. The basic design of the study was to establish chronic hematogenous pyelonephritis in the rat with a strain of Group D streptococci. The rats were then treated with antibiotics to eliminate bacteria. The basic method consisted of the following groups. Pyelonephritic rats: not treated, treated with penicillin, and treated with penicillin and kanamycin (the latter to kill L-forms). Control groups were non-infected rats treated with penicillin or penicillin and kanamycin. Animals were sacrificed at intervals up to 94 weeks after infection, 42 weeks from end of therapy. Calyceal lesions were largely eliminated by antibiotic treatment. Mononuclear cell infiltration, interstitial tubular lesions and papillary lesions were not affected, thus suggesting that viable bacteria are not necessary for persistence of histologic changes of pyelonephritis. Thirty-two strains of Escherichia coli obtained from human kidneys were compared with 34 from bladder infections as to their content of K antigen and ability to ferment galactitol. Neither singly nor together did these two factors correlate with site of infection. However, both of these correlate with mouse virulence as determined by ability to produce pyelonephritis.